Zou Yong, Chen Xi, Xiao Jian, Bo Zhou Dong, Xiao Lu Xiao, Li Wei, Xie Bin, Kuang Xiao, Chen Qiong
Department of Emergency Medicine, Xiangya Hospital of Central South University, Changsha, China.
Department of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, China.
Oncotarget. 2018 Jan 8;9(17):13276-13286. doi: 10.18632/oncotarget.24022. eCollection 2018 Mar 2.
Bacterial lipopolysaccharide (LPS) contributes to airway inflammation and mucus hypersecretion in chronic airway inflammatory diseases, such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). Neutrophil extracellular traps (NETs) are extracellular meshworks composed of DNA fibers and antimicrobial proteins. Although NET formation has been detected in COPD and CF patients, how NETs contribute to these diseases is poorly understood. This study was performed to clarify the effects and mechanisms of action of NETs in airway inflammation and mucus hypersecretion. We created a murine model of LPS-induced airway inflammation and mucus hypersecretion, and found that LPS-induced NET formation was degraded by aerosolized DNase I treatment in mice. Degradation of NETs by aerosolized DNase I reduced LPS-induced airway inflammation and mucus hypersecretion in mice, this reduction correlated with suppression of TLR4/NF-κB signaling pathway. More importantly, NETs promoted LPS-induced production of IL-1β, IL-6 and TNF-α in macrophages. These results suggest NET degradation using aerosolized DNase I is a potential new therapeutic strategy for treating COPD and CF.
细菌脂多糖（LPS）在慢性气道炎症性疾病，如慢性阻塞性肺疾病（COPD）和囊性纤维化（CF）中，会导致气道炎症和黏液分泌过多。中性粒细胞胞外陷阱（NETs）是由DNA纤维和抗菌蛋白组成的细胞外网。虽然在COPD和CF患者中已检测到NET形成，但对NETs如何导致这些疾病却知之甚少。本研究旨在阐明NETs在气道炎症和黏液分泌过多中的作用及作用机制。我们建立了LPS诱导的气道炎症和黏液分泌过多的小鼠模型，发现雾化DNA酶I处理可降解小鼠中LPS诱导的NET形成。雾化DNA酶I降解NETs可减轻小鼠中LPS诱导的气道炎症和黏液分泌过多，这种减轻与TLR4/NF-κB信号通路的抑制相关。更重要的是，NETs促进巨噬细胞中LPS诱导的IL-1β、IL-6和TNF-α的产生。这些结果表明，使用雾化DNA酶I降解NETs是治疗COPD和CF的一种潜在新治疗策略。
